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Basic Information ⬇

Author: Heesung Moon, MD and Uyen T. Lam, MD

Definition

Mitral regurgitation (MR) is retrograde blood flow into the left atrium resulting from any part of an incompetent mitral valve apparatus. This condition may cause left ventricular (LV) failure, as well as increased left atrial and pulmonary pressures leading to pulmonary hypertension and right-sided heart failure.

Synonyms

  • Mitral insufficiency
  • MR
ICD-10CM CODES
I34.0Nonrheumatic mitral (valve) insufficiency
I05.1Rheumatic mitral insufficiency
I05.9Mitral valve disease, unspecified
I05.2Rheumatic mitral stenosis with insufficiency
Q23.3Congenital mitral insufficiency
Epidemiology & Demographics

Mitral regurgitation is a common valvular abnormality occurring in about 10% of the total population. The incidence of MR has increased over that past few decades. However, this may be due to increasing availability of echocardiography leading to MR diagnosis rather than to an actual increase in the prevalence of this condition.

Physical Findings & Clinical Presentation

Heart sounds:

  • Diminished S1 as valve leaflets fail to coapt properly
  • Widely split S2 as A2 occurs earlier because of decreased LV ejection time
  • Presence of an S3 as a result of increased flow into a dilated LV caused by severe MR with systolic impairment

Heart murmurs:

  • Holosystolic, high-pitched, "blowing" murmur is most easily audible at apex with radiation to base, left axilla, or back. There is a poor correlation between the intensity of the systolic murmur and the degree of regurgitation. However, an early diastolic to mid-diastolic rumble (pseudomitral stenosis) suggests severe MR. The murmur of acute MR may be short and unimpressive. This is because the sudden volume overload increases left atrial and pulmonary venous pressures leading to pulmonary congestion and hypoxia, whereas decreased blood delivery to the tissues with concomitant decrease in LV systolic pressure limits the pressure gradient driving MR to early systole.
  • Hyperdynamic apex, sometimes with palpable LV lift and apical thrill.
  • Symptomatic patients with MR generally present with the following:
    1. Symptoms suggestive of heart failure (fatigue, dyspnea, orthopnea, paroxysmal nocturnal dyspnea, edema)
    2. Hemoptysis (caused by pulmonary hypertension)
    3. Atrial fibrillation
Etiology (Fig. E1

Primary MR:

  • Idiopathic myxomatous degeneration of the mitral valve, mitral valve prolapse (most common cause of MR in industrialized countries)1
  • Papillary muscle dysfunction or rupture (typically as a result of an inferior wall myocardial infarction)
  • Ruptured chordae tendineae
  • Infective endocarditis
  • Calcified mitral valve annulus
  • Rheumatic valvulitis (may be combined with mitral stenosis; common in developing countries)
  • Systemic lupus erythematosus (Libman-Sacks endocarditis)
  • Drugs: Fenfluramine, dexfenfluramine, pergolide, cabergoline
  • Congenital cleft valve
  • Radiation heart disease
  • Ischemic MR due to papillary muscle dysfunction from multivessel coronary artery disease (CAD)

Figure E1 Pathophysiologic Triad Approach to Mitral Regurgitation (MR) and its Multifactorial Etiology

The mechanism of leaflet dysfunction defines the three types of MR.

(From Castillo JG, Adams DH: Mitral valve repair and replacement. In Otto CM, Bonow RO (eds): Valvular heart disease: a companion to Braunwald’s heart disease, Philadelphia, 2013, Saunders, pp. 327-340. In Libby P et al: Braunwald’s heart disease, a textbook of cardiovascular medicine, ed 12, Philadelphia, 2022, Elsevier.)

Secondary MR:

  • Hypertrophic cardiomyopathy
  • LV dilation (e.g., secondary to dilated cardiomyopathy)

Diagnosis ⬆ ⬇

Differential Diagnosis

  • Hypertrophic cardiomyopathy
  • Tricuspid regurgitation
  • Aortic stenosis
  • Aortic sclerosis
  • Ventricular septal defect
  • Atrial septal defect
Workup

  • Diagnostic workup consists of echocardiography, ECG, and chest radiograph; cardiovascular magnetic resonance (CMR) and cardiac catheterization are sometimes needed to confirm severity of the disease.
  • Brain natriuretic peptide (BNP) level may be used as a complementary tool in addition to echocardiography to identify patients who may need surgical management rather than conservative treatment. Recent studies suggest that in patients with severe asymptomatic MR, normal LV function and elevations of BNP >105 pg/ml have an independent and additive prognostic value that may identify high-risk patients and aid in the selection of patients for early surgery. However, cutoff value for BNP has not been clearly established.2
Imaging Studies

  • Echocardiography (Fig. E2): Transthoracic echocardiography (TTE) is the initial imaging modality of choice, with TEE performed if insufficient or discordant information is obtained from TTE3. Findings include dilated left atrium, hyperdynamic left ventricle, erratic motion of the leaflet in patients with ruptured chordae tendineae, and color flow Doppler with evidence of MR. The most important aspect of the echocardiographic examination is the quantification of the severity of MR. A vena contracta width ≥0.7 cm, a regurgitant volume ≥60 ml, regurgitant orifice area ≥0.40 cm2 by proximal isovelocity surface area (PISA), and systolic pulmonary vein flow reversal are all echocardiographic criteria of severe MR.
  • Chest x-ray examination:
    1. Left atrial enlargement, LV enlargement
    2. Possible pulmonary congestion, although most often normal
  • ECG:
    1. Left atrial enlargement
    2. LV hypertrophy
    3. Atrial fibrillation
  • Cardiac catheterization: To confirm severity of MR, or to rule out presence of coronary artery disease in patients being evaluated for surgical replacement. Can also be considered in cases where there is discrepancy between symptomatic status and other noninvasive testing.3
  • CMR imaging: Can be considered in cases where echocardiography is limited or LV function/dimensions are borderline, or when clinical condition and echocardiographic findings are discordant.3

Figure E2 Mitral regurgitation.

Four panels depicting varying degrees of mitral regurgitation; the two top panels are apical four-chamber transthoracic views showing, on the left, mild mitral regurgitation and, on the right, moderate to severe mitral regurgitation. On the left, note the relatively narrow jet directed from the tips of the mitral valve toward the posterior left atrial wall. On the right, note the larger jet, filling approximately 40% of the left atrial cavity. The two bottom panels are transesophageal echocardiograms. On the left, note the mitral regurgitation occurring in two discrete jets and, on the right, the highly eccentric jet, which courses along the extreme lateral wall of the left atrium. LA, Left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.

(From Kang DH et al: Comparison of early surgery versus conventional treatment in asymptomatic severe mitral regurgitation, Circulation 119:797-804, 2009. In Libby P et al: Braunwald’s heart disease, a textbook of cardiovascular medicine, ed 12, Philadelphia, 2022, Elsevier.)

Treatment

Treatments can vary depending on chronicity and the severity of MR. In chronic MR, distinguishing between primary and secondary MR is pertinent for management.

Nonpharmacologic Therapy

  • Salt restriction
  • Surgical repair or replacement (see "Acute General Rx" and "Chronic Rx")
Acute General Rx
Acute MR:

  • Medical Therapy:
    1. In acute MR, intravenous vasodilators (such as sodium nitroprusside or nicardipine) has shown some utility. However, the use of vasodilators is limited by hypotension with decreased peripheral resistance.
    2. Afterload reduction can also be achieved by intraaortic balloon counter pulsation. Use of percutaneous circulatory assist device can be used to establish hemodynamic stability before procedure.
  • Surgical Intervention: For acute severe MR, mitral valve surgery, preferably mitral valve repair, is critical. Most patients, especially those with severe MR due to complete papillary muscle rupture, require early surgical intervention for correction of hemodynamic status and symptoms (Class I recommendation).
Chronic Rx
Chronic Primary MR:

  • Medical Therapy: While useful in acute severe MR, there is no evidence of vasodilator reducing severity in chronic primary MR. Guideline-directed medical therapy (GDMT) can be helpful in patients who are unable to undergo surgery to treat LV dysfunction. Stages of chronic primary mitral regurgitation are outlined in Table E1. Fig. 3 and Table E2 illustrate management strategy for intervention for primary MR.
  • Surgical Intervention: Surgery is the only definitive treatment for MR. Although no randomized trial of mitral valve repair vs. replacement exists, repair is favored over replacement4 in degenerative mitral valve disease due to its lower perioperative risk, improved event-free survival, freedom from complications of prosthetic valves, and better postoperative LV function.
  • Surgery is a class I recommendation in patients with the following diagnoses:
    1. Symptomatic patients with severe primary MR irrespective of LV systolic function.
    2. Asymptomatic patients with severe primary MR and LV systolic dysfunction (left ventricular ejection fraction [LVEF] ≤60%) or progressive dilation (left ventricular end-systolic diameter [LVESD] ≥40 mm).
  • Surgery is a class IIa recommendation in:
    1. Asymptomatic severe MR with normal LV systolic function (LVEF ≥60% and LVESD ≤40 mm) in whom the likelihood of successful repair without residual MR is >95% and operative mortality is <1%.
    2. Severely symptomatic patients (New York Heart Association [NYHA] class III/IV) with primary severe MR and high surgical risk, transcatheter edge to edge repair is reasonable if patient life expectancy is at least 1 yr.
  • Surgery is a class IIb recommendation in:
    1. Asymptomatic patients with severe primary MR and normal LV systolic function but with progressive increase in LV size or decrease in ejection fraction (EF) on three or more serial imaging studies.
    2. Symptomatic patients with severe primary MR due to rheumatic valve disease, mitral valve repair may be considered if surgical treatment is indicated and successful repair is likely.

Figure 3 Management strategy for intervention for primary mitral regurgitation.

Colors correspond to Table E2. CVC, Comprehensive valve center; ERO, effective regurgitant orifice; ESD, end-systolic dimension; LVEF, ejection fraction; MR, mitral regurgitation; MV, mitral valve; MVR, mitral valve replacement; RF, regurgitant fraction; RVol, regurgitant volume; VC, vena contracta.

(From Otto CM et al: 2020 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, J Am Coll Cardiol 77:e25-e197, 2021. In Libby P et al: Braunwald’s heart disease, a textbook of cardiovascular medicine, ed 12, Philadelphia, 2022, Elsevier.)

TABLE E1 Stages of Chronic Primary Mitral Regurgitation

StageDefinitionValve AnatomyValve Hemodynamics*Hemodynamic ConsequencesSymptoms
AAt risk for MR
  • Mild MVP with normal coaptation
  • Mild valve thickening and leaflet restriction
  • No MR jet or small central jet area <20% LA on Doppler
  • Small vena contracta <0.3 cm
NoneNone
BProgressive MR
  • Moderate to severe MVP with normal coaptation
  • Rheumatic valve changes with leaflet restriction and loss of central coaptation
  • Previous IE
  • Central jet MR 20%-40% LA or late systolic eccentric jet MR
  • Vena contracta <0.7 cm
  • Rvol <60 ml
  • RF <50%
  • ERO <0.40 cm 2
  • Angiographic grade 1-2+
  • Mild LA enlargement
  • No LV enlargement
  • Normal pulmonary pressure
None
CAsymptomatic severe MR
  • Severe MVP with loss of coaptation or flail leaflet
  • Rheumatic valve changes with leaflet restriction and loss of central coaptation
  • Previous IE
  • Thickening of leaflets with radiation heart disease
  • Central jet MR >40% LA or holosystolic eccentric jet MR
  • Vena contracta ≥0.7 cm
  • Rvol ≥60 ml
  • RF ≥50%
  • ERO ≥0.40 cm 2
  • Angiographic grade 3-4+
  • Moderate or severe LA enlargement
  • LV enlargement
  • Pulmonary hypertension may be present at rest or with exercise.
  • C1: LVEF >60% and LVESD <40 mm
  • C2: LVEF ≤60% and LVESD ≥40 mm
None
DSymptomatic severe MR
  • Severe MVP with loss of coaptation or flail leaflet
  • Rheumatic valve changes with leaflet restriction and loss of central coaptation
  • Previous IE
  • Thickening of leaflets with radiation heart disease
  • Central jet MR >40% LA or holosystolic eccentric jet MR
  • Vena contracta ≥0.7 cm
  • Rvol ≥60 ml
  • RF ≥50%
  • ERO ≥0.40 cm 2
  • Angiographic grade 3-4+
  • Moderate or severe LA enlargement
  • LV enlargement
  • Pulmonary hypertension present
  • Decreased exercise tolerance
  • Exertional dyspnea

ERO, Effective regurgitant orifice; IE, infective endocarditis; LA, left atrium; LV, left ventricle; LVEF, left ventricular ejection fraction; LVESD, left ventricular end-systolic dimension; MR, mitral regurgitation; MVP, mitral valve prolapse; RF, regurgitant fraction; Rvol, regurgitant volume.

* Several valve hemodynamic criteria are provided for assessment of MR severity, but not all criteria for each category will be present in each patient. Classification of MR severity as mild, moderate, or severe depends on data quality and integration of these parameters in conjunction with other clinical evidence.

From Otto CM et al: 2020 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, J Am Coll Cardiol 77:e25-197, 2021. In Libby P et al: Braunwald’s heart disease, a textbook of cardiovascular medicine, ed 12, Philadelphia, 2022, Elsevier.

TABLE E2 Recommendations for Intervention for Chronic Primary Mitral Regurgitation

CorLoeRecommendations
1B-NR
  1. In symptomatic patients with severe primary MR (stage D), mitral valve intervention is recommended irrespective of LV systolic function.
1B-NR
  1. In asymptomatic patients with severe primary MR and LV systolic dysfunction (LVEF ≤60%, LVESD ≥40 mm) (stage C2), mitral valve surgery is recommended.
1B-NR
  1. In patients with severe primary MR for whom surgery is indicated, mitral valve repair is recommended in preference to mitral valve replacement when the anatomic cause of MR is degenerative disease, if a successful and durable repair is possible.
2aB-NR
  1. In asymptomatic patients with severe primary MR and normal LV systolic function (LVEF ≥60% and LVESD ≤40 mm) (stage C1), mitral valve repair is reasonable when the likelihood of a successful and durable repair without residual MR is >95% with an expected mortality rate of <1%, when it can be performed at a primary or comprehensive valve center.
2bC-LD
  1. In asymptomatic patients with severe primary MR and normal LV systolic function (LVEF >60% and LVESD <40 mm) (stage C1) but with a progressive increase in LV size or decrease in EF on ≥3 serial imaging studies, mitral valve surgery may be considered irrespective of the probability of a successful and durable repair.
2aB-NR
  1. In severely symptomatic patients (NYHA Class III or IV) with primary severe MR and high or prohibitive surgical risk, transcatheter edge-to-edge repair (TEER) is reasonable if mitral valve anatomy is favorable for the repair procedure and patient life expectancy is at least 1 yr.
2bB-NR
  1. In symptomatic patients with severe primary MR attributable to rheumatic valve disease, mitral valve repair may be considered at a comprehensive valve center by an experienced team when surgical treatment is indicated, if a durable and successful repair is likely.
3: HarmB-NR
  1. In patients with severe primary MR in which leaflet pathology is limited to less than half the posterior leaflet, mitral valve replacement should not be performed unless mitral valve repair has been attempted at a primary or comprehensive valve center and was unsuccessful.

EF, Ejection fraction; LV, left ventricle; LVEF, LV ejection fraction; LVESD, LV end-systolic dimension; MR, mitral regurgitation; NYHA, New York Heart Association.

From Otto CM et al: 2020 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, J Am Coll Cardiol 77:e25-197, 2021. In Libby P et al: Braunwald’s heart disease, a textbook of cardiovascular medicine, ed 12, Philadelphia, 2022, Elsevier.

Chronic Secondary MR:

  • Medical Therapy: Because secondary MR usually develops due to LV systolic dysfunction, GDMT is mainstay of therapy. It is often responsive to GDMT and reduces the severity of secondary MR. Coronary revascularization or cardiac revascularization can be considered. Stages of chronic secondary mitral regurgitation are outlined in Table E3. Table E4 and Fig. E4 illustrate management strategy for intervention for secondary MR.
  • Surgical Intervention: In chronic secondary MR, appropriate and proper trial with GDMT is crucial before determining necessity for surgical or transcatheter interventions.
  • Surgery is a class IIa recommendation in:
    1. Chronic severe secondary MR related to LV systolic dysfunction of EF <50% with persistent symptoms (NYHA class II/III/IV) while on optimal GDMT for HF. If mitral anatomy is favorable on TEE, transcatheter edge-to-edge repair (TEER) is reasonable.
    2. Severe secondary MR when coronary artery bypass graft (CABG) was undertaken for myocardial ischemia.
  • Surgery is a class IIb (reasonable) recommendation in:
    1. Chronic severe secondary MR from atrial annular dilation with EF ≥50% with severe persistent symptoms (NYHA class III/IV) despite therapy for heart failure (HF), atrial fibrillation (AF), or other comorbidities.
    2. Chronic severe secondary MR with LEVF<50% and persistent severe symptoms (NYHA class III/IV) on optimal GDMT. In these patients with CAD, chordal sparing MV replacement may be reasonable over downsized annuloplasty repair.

Figure E4 Management strategy for intervention for secondary mitral regurgitation.

Colors correspond to Table E4. AF, Atrial fibrillation; CABG, coronary artery bypass graft; ERO, effective regurgitant orifice; GDMT, guideline-directed management and therapy; HF, heart failure; LVEF, left ventricular ejection fraction; LVESD, left ventricular end-systolic dimension; MR, mitral regurgitation; MV, mitral valve; PASP, pulmonary artery systolic pressure; RF, regurgitant fraction; Rvol, regurgitant volume; Rx, medication.

(From Otto CM et al: 2020 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, J Am Coll Cardiol 77:e25-197, 2021. In Libby P et al: Braunwald’s heart disease, a textbook of cardiovascular medicine, ed 12, Philadelphia, 2022, Elsevier.)

TABLE E3 Stages of Chronic Secondary Mitral Regurgitation

StageDefinitionValve AnatomyValve Hemodynamics*Associated Clinical FindingsSymptoms
AAt risk of MR
  • Normal valve leaflets, chords, and annulus in a patient with coronary disease or cardiomyopathy
  • No MR jet or small central jet area <20% LA on Doppler
  • Small vena contracta <0.30 cm
  • Normal or mildly dilated LV size with fixed (infarction) or inducible (ischemia) regional wall motion abnormalities
  • Primary myocardial disease with LV dilation and systolic dysfunction
Symptoms attributable to coronary ischemia or HF may be present that respond to revascularization and appropriate medical therapy
BProgressive MR
  • Regional wall motion abnormalities with mild tethering of mitral leaflet
  • Annular dilation with mild loss of central coaptation of the mitral leaflets
  • ERO †<0.40 cm 2
  • Rvol <60 ml
  • RF <50%
  • Regional wall motion abnormalities with reduced LV systolic function
  • LV dilation and systolic dysfunction attributable to primary myocardial disease
Symptoms attributable to coronary ischemia or HF may be present that respond to revascularization and appropriate medical therapy
CAsymptomatic severe MR
  • Regional wall motion abnormalities and/or LV dilation with severe tethering of mitral leaflet
  • Annular dilation with severe loss of central coaptation of the mitral leaflets
  • ERO †≥0.40 cm 2
  • Rvol ≥60 ml
  • RF ≥50%
  • Regional wall motion abnormalities with reduced LV systolic function
  • LV dilation and systolic dysfunction attributable to primary myocardial disease
Symptoms attributable to coronary ischemia or HF may be present that respond to revascularization and appropriate medical therapy
DSymptomatic severe MR
  • Regional wall motion abnormalities and/or LV dilation with severe tethering of mitral leaflet
  • Annular dilation with severe loss of central coaptation of mitral leaflets
  • ERO †≥0.40 cm 2
  • Rvol ≥60 ml
  • RF ≥50%
  • Regional wall motion abnormalities with reduced LV systolic function
  • LV dilation and systolic dysfunction attributable to primary myocardial disease
  • HF symptoms attributable to MR persist even after revascularization and optimization of medical therapy
  • Decreased exercise tolerance
  • Exertional dyspnea

ERO, Effective regurgitant orifice; HF, heart failure; LA, left atrium; LV, left ventricular; MR, mitral regurgitation; RF, regurgitant fraction; Rvol, regurgitant volume.

* Several valve hemodynamic criteria are provided for assessment of MR severity, but not all criteria for each category will be present in each patient. Categorization of MR severity as mild, moderate, or severe depends on data quality and integration of these parameters in conjunction with other clinical evidence.

† The measurement of the proximal isovelocity surface area (PISA) by two-dimensional transthoracic echocardiography (TTE) in patients with secondary MR underestimates the true ERO because of the crescentic shape of the proximal convergence.

From Otto CM et al: 2020 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, J Am Coll Cardiol 77:e25-197, 2021. In Libby P et al: Braunwald’s heart disease, a textbook of cardiovascular medicine, ed 12, Philadelphia, 2022, Elsevier.

TABLE E4 Recommendations for Intervention for Chronic Secondary Mitral Regurgitation

CorLoeRecommendations
2aB-R
  1. In patients with chronic severe secondary MR related to LV systolic dysfunction (LVEF <50%) who have persistent symptoms (NYHA Class II, III, or IV) while on optimal GDMT for HF (stage D), TEER is reasonable in patients with appropriate anatomy as defined on TEE and with LVEF between 20% and 50%, LVESD ≤70 mm, and pulmonary artery systolic pressure ≤70 mm Hg.
B-NR
  1. In patients with severe secondary MR (stages C and D), mitral valve surgery is reasonable when CABG is undertaken for the treatment of myocardial ischemia.
2bB-NR
  1. In patients with chronic severe secondary MR from atrial annular dilation with preserved LV systolic function (LVEF ≥50%) who have severe persistent symptoms (NYHA Class III or IV) despite therapy for HF and therapy for associated AF or other comorbidities (stage D), mitral valve surgery may be considered.
B-NR
  1. In patients with chronic severe secondary MR related to LV systolic dysfunction (LVEF <50%) who have persistent severe symptoms (NYHA class III or IV) while on optimal GDMT for HF (stage D), mitral valve surgery may be considered.
B-R
  1. In patients with CAD and chronic severe secondary MR related to LV systolic dysfunction (LVEF <50%) (stage D) who are undergoing mitral valve surgery because of severe symptoms (NYHA class III or IV) that persist despite GDMT for HF, chordal-sparing mitral valve replacement may be reasonable to choose over downsized annuloplasty repair.

CABG, Coronary artery bypass graft; CAD, coronary artery disease; GDMT, guideline-directed medical therapy; HF, heart failure; LVEF, left ventricular ejection fraction; LVESD, left ventricular end-systolic dimension; MR, mitral regurgitation; NYHA, New York Heart Association; TEE, transesophageal echocardiography; TEER, transcatheter edge-to-edge repair.

Disposition

Prognosis is generally good unless there is significant impairment of LV function or significantly elevated pulmonary artery pressures. Most patients remain asymptomatic for many years (average interval from diagnosis to onset of symptoms is 16 yr). In patients with chronic severe MR, MR is commonly progressive, with onset of other symptoms or LV dysfunction within 6 to 10 yr. However, surgery should be advised well before the onset of symptoms in case of worsening LVEF and LV systolic dimensions and presence of pulmonary hypertension or atrial fibrillation, all of which are poor prognostic signs.

Referral

  • Surgical referral in selected patients (see "Acute General Rx" and "Chronic Rx").
  • Emergency surgery is usually necessary in patients with acute MR caused by ruptured papillary muscle or chordae tendineae after myocardial infarction.
  • Mitral valve repair can also be accomplished with percutaneous implantation of a MitraClip device in patients who are too high risk for surgery.

Pearls & Considerations ⬆ ⬇

Comments

  • Although vasodilators and other agents should be used to treat hypertension in patients with severe MR, there is no evidence that they will delay the need for eventual valve surgery, which is the definitive treatment for severe MR.
  • In 2007, the American Heart Association guidelines for prevention of infectious endocarditis were revised, and routine antibiotic prophylaxis to undergo dental or other invasive procedures is no longer recommended, unless the patient has had prior endocarditis.
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    2. Gallo G : Functional role of natriuretic peptides in risk assessment and prognosis of patients with mitral regurgitationdoi:10.3390/jcm9051348J Clin Med. 9(5):1348, 2020.
    3. Otto CM : 2020 ACC/AHA guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice GuidelinesCirculation. 143:e7-e227, 2021.
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